The rhizosphere soil microenvironment critically influences secondary metabolite accumulation in medicinal rhizomatous plants. To compare the effects of the rhizosphere soil microenvironment in major production areas of Sichuan province on the accumulation of secondary metabolites in turmeric, we collected turmeric from Qianwei, Shuangliu, and Xingwen production areas in Sichuan province as research subjects. UPLC-Q-TOF-MS-based metabolomics was employed to analyze the composition of metabolites. And the high-throughput sequencing platform was utilized to analyze the rhizosphere soil microbial community structure. Then correlation analyses were performed between the metabolites, microbial community, and physicochemical factors. The results indicated that the metabolite profiles of turmeric from different production areas are relatively similar. The most abundant secondary metabolites in plants include ketones, aldehydes, esters, terpenoids, flavonoids, and polyphenols. Polyphenols, terpenoids, and some curcuminoids were significantly higher in turmeric from Shuangliu region than in samples from Qianwei and Xingwen. Significant differences were observed in rhizosphere soil physicochemical properties, including pH, organic matter, total nitrogen, available phosphorus, available potassium, manganese, magnesium, calcium, copper, and selenium among the different regions. At the phylum level, Proteobacteria and Acidobacteria were the dominant bacterial phyla across all three regions, while considerable variations existed at the genus level. In turmeric, correlation analysis revealed that bisdemethoxycurcumin correlated positively with pH, manganese, magnesium, and calcium. ar-Turmerone correlated positively with organic matter and available phosphorus. And tetrahydrocurcumin correlated positively with Rhodanobacter and Sphingomonas. In summary, secondary metabolites differed between turmeric from different regions. These metabolites exhibited correlations with both the physicochemical properties of the rhizosphere soil and the associated microbial communities. These findings provide a scientific basis for cultivation base selection and ecosystem-based cultivation practices.

The heat shock transcription factor (HSF) family plays a crucial role in plant growth, development, and responses to biotic and abiotic stresses. As a traditional Chinese herbal medicine, Glycyrrhiza uralensis Fisch. is rich in various bioactive compounds, including flavonoids and terpenes. However, a systematic identification and characterization of the HSF gene family in G. uralensis is currently lacking. To clarify the biological functions of this gene family, we systematically identified HSF family members based on the genomic data of G. uralensis, and analyzed their physicochemical properties, chromosomal localization, phylogenetic relationships, conserved motifs, and collinearity. Meanwhile, combined with transcriptome sequencing and qRT-PCR analyses, we elucidated the expression patterns of GuHSF genes and their co-expressed genes associated with flavonoid biosynthesis under drought stress. The results showed that a total of 26 GuHSF genes were identified from the genome of G. uralensis, which can be classified into three subfamilies, and the HSF proteins within the C subfamily exhibited high similarity in conserved motifs. Collinearity analysis revealed 12 pairs of segmental duplications within the GuHSF family, and the syntenic relationships between GuHSF genes and soybean HSF genes were the strongest among the compared species. The results of qRT-PCR analysis indicated that GuHSF2, GuHSF4, GuHSF14, GuHSF18, GuHSF21, and GuHSF26 genes were significantly induced by drought stress. In addition, under drought conditions, strong correlations were observed between GuHSF1, GuHSF4, GuHSF9, GuHSF11, and GuHSF21 genes and flavonoid biosynthesis-related genes. This study systematically identified and analyzed the GuHSF family genes in G. uralensis, which provides important clues for subsequent investigations into the biological functions of core members of this family.

Sorafenib serves as a first-line treatment for advanced hepatocellular carcinoma (HCC), advanced renal cell carcinoma (RCC), and radioactive iodine-refractory differentiated thyroid carcinoma (DTC). While it improves patient prognosis by inhibiting tumor cell proliferation and angiogenesis, approximately 70% of patients experience limited efficacy within 6 months of treatment due to primary or acquired resistance mechanisms. These mechanisms include abnormal activation of core signaling pathways, epithelial-mesenchymal transition (EMT), dysregulated ferroptosis, aberrant drug transport and metabolism, and abnormal regulation of the tumor microenvironment (TME). Based on resistance mechanism subtypes, this systematic review summarizes recently reported extracts from traditional Chinese medicine (TCM) and natural product monomers that demonstrate the potential to reverse sorafenib resistance. It further provides an in-depth analysis of the current challenges in resistance research. These challenges encompass the mismatch between pharmacokinetic properties and resistance mechanism subtypes (e.g., precipitation of lipophilic components in the acidic TME, metabolic competition), the unclear core targets and cooperative interaction patterns within resistance subtypes (e.g., undefined contribution of multiple mechanisms), and the lack of standardization and continuity in clinical trials and translation (e.g., absence of subtype stratification, disconnection between quality standards and mechanisms). To address these challenges, this review proposes innovative directions, including the development of mechanism-oriented customized drug delivery systems, multi-omics-driven elucidation of core targets and construction of cooperative networks, and the establishment of clinical translation systems stratified by resistance mechanism subtypes. This review aims to provide insights for deepening fundamental research on the combination of TCM/natural products with sorafenib for treating advanced cancer and to promote its standardized clinical application, thereby fostering the development of integrated Chinese-Western medicine strategies in oncology.

Diabetic kidney disease is a significant microvascular complication of diabetes that can progress to end-stage renal disease, severely threatening patients' quality of life and longevity. Its pathogenesis is complex, involving multiple pathways including inflammatory responses, oxidative stress, metabolic disorders, and disrupted intercellular signaling networks in the kidney, all significantly influenced by individual variability. Current clinical treatment options remain limited, with a lack of targeted effective drugs posing substantial challenges for prevention and management. This systematic review examines the pathogenesis and existing treatment strategies for diabetic kidney disease. By integrating recent advances, it explores emerging therapeutic approaches and potential breakthrough directions, aiming to provide a theoretical and practical foundation for innovative interventions and clinical translation.

Liquid-liquid phase separation (LLPS) serves as a key mechanism driving numerous essential biological processes. In eukaryotic cells, LLPS facilitates the formation of membraneless organelles (MLOs) by promoting the local enrichment of biomacromolecules such as proteins and nucleic acids, thereby establishing compartmentalization to enhance biochemical reaction efficiency. Under stress conditions, it also helps protect critical cellular components, including mRNA and proteins. Growing evidence in recent years indicates that LLPS-driven biomolecular condensation similarly occurs in prokaryotes. For instance, under environmental stresses (such as oxidative stress, nutrient deprivation, or antibiotic exposure), bacteria can form biomolecular condensates via LLPS that perform MLOs-like functions, improving the stress adaptability of bacteria. Proposed protective mechanisms include shielding proteins from irreversible inactivation or degradation, activating protein quality control systems, and inducing a dormant state to promote survival. Moreover, under physiological conditions, LLPS is involved in core cellular processes in bacteria, such as plasmid partitioning, chromosome segregation, transcriptional regulation, cell division, DNA replication, and repair. This review systematically summarizes the mechanisms by which biomolecular aggregates form in bacteria under both physiological and stress conditions, with a focus on how LLPS-mediated phase transitions enhance bacterial fitness and environmental adaptability. We also aim to provide insights into novel antibacterial strategies targeting LLPS.

CD4⁺ T cell-mediated immune inflammatory responses play a significant role in the development and progression of atherosclerosis (AS). CD4⁺ T cells can differentiate into multiple subtypes, such as pro-inflammatory Th1/Th17 cells and anti-inflammatory Th2/Treg cells, and the imbalance between these subtypes determines the direction of progression of AS. Increasingly, studies have shown that metabolic reprogramming of CD4⁺ T cells induces their pro-inflammatory differentiation, exacerbates vascular microenvironmental inflammation and plaque instability, and thus promotes the development of AS. In this review, we shall focus on the relationship between CD4⁺ T cell metabolic reprogramming-mediated cellular differentiation, functional alterations, and the onset and progression of AS. We shall also examine therapeutic strategies targeting CD4⁺ T cell metabolism in AS. This will provide evidence for elucidating the mechanisms underlying vascular inflammation in AS and offer guidance for identifying novel targets and approaches for the prevention and treatment of AS in clinical practice.

Metallo-β-lactamases (MBLs) mediate carbapenem antibiotic resistance by hydrolyzing the β-lactam ring. However, existing inhibitors remain largely confined to laboratory research due to poor selectivity or insufficient potency, and no clinically approved MBL inhibitors are currently available. MBLs are categorized into three subclasses B1, B2, and B3. B1 and B3 subclasses possess a binuclear zinc catalytic center, whereas B2 harbors a single active zinc ion. Despite their structurally conserved active sites featuring a characteristic αβ/βα-fold architecture with catalytic zinc ions positioned between αβ units flanked by flexible loops. Meanwhile, candidates developed through enzymatic and thermodynamic studies, such as 2-quinazolinone QDP-1, boronic acid derivatives VNRX-5133/QPX7728, thiazolecarboxylic acid ANT2681, and selenium-containing compound SPI-1005, still face challenges in achieving broad-spectrum efficacy and clinical safety. This review systematically examines the interaction mechanisms between inhibitors and MBLs, focusing on three strategic approaches: Covalent binding strategies, zinc ion chelation, and allosteric inhibition. The synthesis aims to provide theoretical foundations and rational design strategies for developing potent, safe, and broad-spectrum metallo-β-lactamase inhibitors.

Since its introduction to the market, etomidate has held a significant position among intravenous anesthetics due to its favorable anesthetic properties and hemodynamic stability. However, adverse reactions like adrenocortical suppression and myoclonus have limited its clinical application. In recent years, the research on novel etomidate derivatives that can retain the excellent anesthetic characteristics of etomidate while significantly ameliorating its adverse effects has become a hot topic in the development of new anesthetic drugs. Through the structural modification of pharmacophores such as the carboxylic acid ester chain and imidazole ring, new derivatives, including ABP-700, EL-0052, ET-26, and NH600001, have been discovered. Some of these drugs have entered the phase Ⅲ clinical trial or NDA application stage, showing promising prospects for successful development and marketing approval. This article reviews the design strategies, preclinical research, and clinical research progress of etomidate derivatives, aiming to provide references for the development of new intravenous anesthetics.

Calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) is a key enzyme mediating cardiac diseases such as arrhythmia, ischemic heart disease, and heart failure. Its involvement in the progression of cardiac diseases has become increasingly clear with advancing research. Targeted regulation of cardiac CaMKⅡ has become a major therapeutic strategy for heart diseases. However, traditional drug delivery strategies suffer from poor cardiac targeting and low local concentrations, necessitating the integration of innovative delivery and release systems. This review first describes the CaMKⅡ and its role in cardiac diseases, and then provides a systematic review of the design and research progress of cardiac-targeted nanodelivery systems, with the aim of offering new insights into the targeted regulation of cardiac CaMKⅡ and the development of innovative cardiac disease therapies.

Nucleic acid therapeutics, as a transformative modality in modern biopharmaceuticals, mediate disease treatment through precise gene expression modulation. Their remarkable therapeutic potential, such as in oncology, has been demonstrated clinically. The regulatory approval of nucleic acid drugs, exemplified by the SARS-CoV-2 mRNA vaccines, has not only validated their clinical translation potential, but also accelerated advancements in nucleic acid drug development platforms. The functional efficacy of nucleic acid drugs is fundamentally governed by their three-dimensional structural architecture, necessitating rigorous stability assessments throughout the development pipeline. Critical considerations include maintaining native conformation during delivery, achieving target-specific release profiles, and optimizing storage formulations for long-term stability. Circular dichroism (CD) spectroscopy has emerged as an indispensable analytical tool due to its exceptional sensitivity to chiral environments. CD enables precise detection of nucleic acid structural transitions, from base-stacking interactions to complex higher-order conformational changes, making it invaluable for structural characterization. This review summarizes recent research progress on the typical conformational characteristics of nucleic acid drugs and the factors influencing their stability. It focuses particularly on methodological advances in CD spectroscopy for structural analysis and quality control, providing critical insights to guide future research in this rapidly evolving field.